a safety and efficacy study of infusions of hepastem in urea cycle disorders pediatric patients

Conditions: Urea Cycle Disorder

Summary: this is a phase2, prospective, open label study designed to investigate the safety and efficacy of several infusions of hepastem. this study will include 5 pediatric urea cycle disorder (ucd) patients under 12 years old. its assessment includes all safety parameters and an efficacy assessment based on 13c tracer tests, ammonia, medication and diet changes. hepastem will be administered in addition to the conventional ucd treatments.

patient eligibility will be assessed during the screening visit. the investigator should ensure that the chronic metabolic treatment (i.e. balance between low protein diet, supplements in amino acid mix, nitrogen scavenger and supplements in arginine and/or citrulline) of the patient is optimized for his/her metabolic condition. during the baseline period, 3 study visits will take place at 6 weeks interval for assessing the metabolic condition and the chronic metabolic treatment of the patient. a calculated dose based on patient's body weight will be administered via permanent mesenteric portal access and catheter for four times or a transient percutaneous transhepatic catheter for three times. the follow-up period will start approximately 12 weeks after the first hepastem infusion day. this period will last approximately 9 months. study visits will take place every 1.5month, fu visit 1 to fu visit 7. primary objective: 1. to demonstrate the functional efficacy of hepastem at 6 months after initiation of infusion in terms of ureagenesis improvement based on a functional test (13c tracer method) 2. to evaluate the safety of hepastem up to one year after initiation the hepastem infusion secondary objective: 1. to evaluate the efficacy of hepastem in terms of functional, clinical, and biochemical parameters up to one year after initiation of the infusion.

Eligibility criteria:
inclusion criteria: * the patient is a pediatric patient \<12 years * the patients presents with one of the following ucds. (cps1d, otcd, assd, asld, argd) * the patient has severe disease with impaired protein tolerance defined as: chronic protein restricted diet and chronic treatment with at lease one nitrogen scavenger. * the patient shows patency of the portal vein and its branches including mesenteric veins, with normal flow velocity as confirmed by doppler us and accessibility of the portal vein and/or affluents. * the patient (if capable of signing) and parents or legal representative have signed a written informed consent form. exclusion criteria: * the patient presents acute liver failure. * the patient presents clinical or radiological evidence of liver cirrhosis. * the patient presents or has a history of hepatic or extrahepatic malignancy. * the patient has a known clinically significant cardiac malformation. * the patient has a personal history of venous thrombosis, or has a clinically significant abnormal value for protein s, protein c, anti-thrombin iii, and/or activated protein c resistance (apcr) at screening. in case of known family history, a complete coagulation work-up should be performed. in all above described cases, results need to be discussed with sponsor before enrolling the patient in the study. * patient currently receiving other unapproved investigational drug or device. * the patient underwent previous mature liver cell or stem cell transplantation or received an organ liver transplant or received hepastem infusion. * the patient has a contraindication to methylprednisolone, tacrolimus. * the patient has a known hypersensitivity or allergy to heparin. * the patient has a known hypersensitivity or allergy to the antibiotics preventing post-operative infections that are prescribed according to institutional guidelines, and no alternative prophylaxis can be found. * the patient had or has a renal insufficiency treated by dialysis. * the patient requires valproate therapy. * the patient has a known hypersensitivity or allergy to contrast agents (if applicable) that cannot be treated adequately. * the patient has a thrombosis of the portal vein or persisting impairment of anterograde portal blood flow. * the patient has a porto systemic shunt or fistula assessed by doppler us or an arantius channel or protal hypertension. * the site where the catheter is intended to be placed has previously suffered from venous thrombosis or vascular surgical procedures. * the patient has an ongoing infection or suffered from an infection in the last 2 weeks (including active ebv infection at screening). the patient may be enrolled after resolution of the infection. * there is any significant condition or disability that, in the investigator's opinion, may interfere with the patient's participation in the study.

Keywords: urea cycle disorder hyperammonemia metabolic decompensation